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A.R. Mato et al.
Table 1. Positron emission tomography-computed tomography findings and baseline characteristics for screened patients. Screened patients
PET-CT findings at screening
Number of FDG-avid nodes,* median (range) SUVmax, median (range)
SUVmax ≥10
Baseline patient characteristics
Age, median (range), years
N. of prior therapies, median (range)
N=167
5 (1 – 12) 5 (0 – 73) 25 (15)
67 (28 – 85)
4 (1 – 15) 104 (62)
55 (33)
37 (22)
104 (62)
146 (87) / 56 (34) 75 (45) / 124 (74) 69 (41)
17 (10)
3.4 (0 – 59.6) 111/164 (68)
93/118 (79) 69/166 (42) 56/165 (34) 48/161 (30) 70/155 (45) 45/125 (36)
Ibrutinib, n (%)
Idelalisib, n (%)
Ibrutinib and idelalisib, n (%)
Purine analogs, n (%)
Rituximab/other monoclonal antibodies, n (%) Bendamustine/other alkylating agents, n (%)
Bulky nodes ≥5 cm, n (%)
Bulky nodes ≥10 cm, n (%)
β-2 microglobulin,‡ median (range), mg/L
Lactate dehydrogenase above the upper limit of normal,‡ n/N (%)
Prognostic factors,‡ n/N (%) Unmutated IGHV
del(17p)
del(11q)
TP53 mutation
CD38 positive
ZAP-70 positive
PET-CT: positron emission tomography-computed tomography; FDG: 18-F-fluorodeoxyglucose, SUVmax: maximum standardized uptake value of FDG. *PET-avid defined as SUV >3 per nuclear medicine ranges provided by participating institutions. ‡Site reported data; presented for all patients with available data. N/n: number.
(SAS Institute Inc., Cary, NC) was used to generate all statistical summaries. Unless otherwise stated, statistical analyses were 2- sided with P≤0.05 considered significant.
Results
Patients' characteristics
A total of 167 BCRi-failure patients were screened for this study (Online Supplementary Figure S1). There were 40 patients who were screened but did not proceed in the study:20 27 failed to meet inclusion criteria per study pro- tocol [most commonly due to inadequate liver or renal function (n=9), biopsy confirmed RT (n=7), and inade- quate bone marrow function (n=5)], nine withdrew con- sent (for different reasons), and four did not participate for other reasons [investigator decision, second primary malignancy discovered on screening (not RT), spleen biop- sy required to assess for RT but not recommended by investigator, congestive heart failure (n=1 each)]. Demographics and baseline characteristics for all screened patients are presented in Table 1. Patients had received a median of four prior therapies (range: 1-15), 42% of patients with available data had chromosome 17p dele- tion (del[17p]), 30% had TP53 mutation, and 79% had unmutated IGHV.
Positron emission tomography-computed tomography imaging and biopsy at screening
Of the 167 screened patients, 84 (50%) had a lymph node with SUVmax ≥5 and 25 (15%) patients had SUVmax ≥10 (Table 1).3,9 Following PET-CT imaging, 57 patients met protocol criteria for the required core biopsy of the FDG-avid lymph node to evaluate for RT, of whom 22 failed screening for other reasons and did not have a biopsy. (Other reasons for screen failure were heteroge- neous and have been previously reported20) (Online Supplementary Figure S1). Of the remaining 35 patients who underwent biopsy, 19 had SUVmax ≥10 and 16 had SUVmax <10 with other high risk clinical/laboratory fea- tures that mandated biopsy. Additionally, one patient had an abnormal CT result prior to study-related procedures which led to biopsy of a node during screening (patient did not have PET-CT at screening). Eight patients had RT: 22% of all patients who were biopsied (n=36) and 4.8% of all 167 patients progressing after BCRi screened for this clinical trial (all DLBCL). These eight patients were not enrolled on the clinical trial (Table 2), three failed screen- ing due to other reasons including other malignancies (metastatic anal cancer and neuroendocrine tumor), and 25 patients had a biopsy demonstrating CLL without transformation and were subsequently enrolled on study. Of the eight patients with biopsy-confirmed RT, five had
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